超音波刺激裝置設計與模擬

The design and simulation of ultrasonic stimulation devices

林宇宣(Yu-Xuan Lin)

指導教授 ： 王兆麟

國立臺灣大學/工學院/醫學工程學研究所/碩士(2021年)

https://doi.org/10.6342/NTU202102108

摘要

超音波因指向性好、空間解析度高等優點，已大量應用在醫學領域上，而其中低能量超音波提供非侵入性的力學刺激，且具備不會產生嚴重熱效應的好處，故已被用來對細胞、組織甚至活體動物進行大量研究，惟各實驗室自行使用的超音波刺激設備仍有架設過於複雜、聲強度及刺激方式差異大、對生物研究人員操作不友善等問題，尤其是非工程的生物研究人員在使用或架設這些設備上往往會遇到困難，故本研究希望針對這些問題進行改善，自行開發一系列結構緊湊、便於使用且聲強度及刺激方式皆類似的超音波設備，協助生物研究人員進行研究。
而本研究成果共開發出兩套體外實驗設備，分別為Live Image Chamber mini (mini-LIC)、Live Image Chamber Pro (LIC-Pro)以及一套體內實驗設備Focus ultrasound lens。在需要避免溫度效應且大量實驗下可選擇使用mini-LIC，若是需要研究較高強度影響可選擇使用LIC-Pro，若是需要研究超音波對大腦特定區域之神經調控，可選擇使用Focus ultrasound lens，然而這些設備能夠應用的範圍遠遠不止於此，可根據研究人員的不同需要延伸其適用範圍，如將玻璃蓋玻片替換為石英蓋玻片，即可研究壓電效應對細胞之影響，亦或是組合不同中心頻率的超音波裸片來對細胞進行複合刺激，故這些設備可以因應研究方向作靈活地做修改，以滿足研究人員所需。
另外，超音波設備由於本身會涉及聲學、固體力學及電學三個物理耦合，具有較複雜的現象在內，故本研究另一主軸便是以詳細地步驟替各設備建立有限元素模型，這些模型可以被視為是虛擬化的設備，有了這些模型研究人員便可透過模擬更深入了解設備原理或尺寸設計變更之影響。
而本研究也探討較長時間之壓電刺激對類神經細胞N2a產生的影響並觀察其生長之狀況，此外我們也實際對LIC進行修改，將種有N2a細胞蓋玻片下放入半片玻璃及半片石英，以保證每盤細胞皆在相同環境下接受刺激並比較兩邊之差異，如此便可增加實驗可信度。由實驗結果發現壓電刺激確實會影響N2a細胞生長錐動態行為，導致其活動程度增加並使整個細胞生長，同時此研究也間接證明上述設備確實具有靈活修改使用方式之特性。

關鍵字

超音波刺激 ； 壓電刺激 ； 有限元素法 ； 微能量超音波

並列摘要

Ultrasonic waves have been widely used in the medical field because of the good directivity and high spatial resolution. Moreover, low-intensity ultrasound provides non-invasive mechanical stimulation without thermal effects, so it has been used to conduct a lot of research on cells, tissues and even living animals. However, the ultrasonic stimulation devices in each laboratory still have some problems such as complicated installation, large variation in sound intensity and stimulation method, and unfriendly operation, especially for those researchers without engineering background. Therefore, this research hopes to address on these problems and develop a series of ultrasonic devices that are compact-in-design, easy to use, and consistent in generating sound intensity.
We have developed two sets of in-vitro devices, namely Live Image Chamber mini (mini-LIC), Live Image Chamber Pro (LIC-Pro) and one set of in-vivo devices called focus ultrasound lens. Mini-LIC can be used when temperature effects need to be avoided and massive experiments are needed. LIC-Pro can be used to study the effects of higher intensity than mini-LIC. Focus ultrasound lens is suitable for the study of neuromodulation of ultrasound on specific areas of the brain. However, the scope of applications of these devices is much more than that. Researchers can expand the scope of application according to different situations, such as replacing glass coverslips with quartz coverslips, studying piezoelectric stimulation to cells, or combining piezoelectric ceramics with different center frequencies to generate stimulation. These devices can be flexibly modified to meet the needs of researchers.
In addition, the ultrasonic stimulation devices involve three physical couplings of acoustics, solid mechanics, and electricity, and has more complex phenomena inside. Thus, the other main goal of this research is to establish finite element models for each device in detailed steps. These models can be regarded as virtualized devices which can help researchers to have a deeper understanding of principles in devices or observe differences caused by parameter change.
We also study the effects of piezoelectric stimulation on N2a cells. To ensure each coverslip with cells is stimulated in the same environment, we modified the LIC by placing a half glass coverslip and a half quartz coverslip under the coverslip with cells, so the differences between the two sides are compared, which can increase the reliability of the experiment. The result shows that piezoelectric stimulation does affect the dynamic behavior of N2a cell's growth cones, resulting in increased activity and growth of the entire cell. At the same time, this study also indirectly proves that our devices do have the advantage of flexible modification to meet different situations.

並列關鍵字

Ultrasound stimulation ； Piezoelectric stimulation ； Finite element method ； very-low-intensity ultrasound

參考文獻

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